Genetic analysis of Italian patients with congenital tufting enteropathy

BACKGROUND: Congenital tufting enteropathy (CTE), an inherited autosomal recessive rare disease, is a severe diarrhea of infancy which is clinically characterized by absence of infl ammation and presence of intestinal villous atrophy. Mutations in the EpCAM gene were identified to cause CTE. Recent cases of syndromic tufting enteropathy harboring the SPINT2 (19q13.2) mutation were described. METHODS: Four CTE Italian patients were clinically and immunohistochemically characterized. Direct DNA sequencing of EpCAM and SPINT2 genes was performed. RESULTS: All patients were of Italian origin. Three different mutations were detected (p.Asp219Metfs*15, Tyr186Phefs*6 and p.Ile146Asn) in the EpCAM gene; one of them is novel (p.Ile146Asn). Two patients (P1 and P2) showed compound heterozygosity revealing two mutations in separate alleles. A third patient (P3) was heterozygous for only one novel EpCAM missense mutation (p.Ile146Asn). In a syndromic patient (P4), no deleterious EpCAM mutation was found. Additional SPINT2 mutational analysis was performed. P4 showed a homozygous SPINT2 mutation (p.Y163C). No SPINT2 mutation was found in P3. CLDN7 was also evaluated as a candidate gene by mutational screening in P3 but no mutation was identifi ed. CONCLUSIONS: This study presented a molecular characterization of CTE Italian patients, and identified three mutations in the EpCAM gene and one in the SPINT2 gene. One of EpCAM mutations was novel, therefore increasing the mutational spectrum of allelic variants of the EpCAM gene. Molecular analysis of the SPINT2 gene also allowed us to identify a SPINT2 substitution mutation (c.488A>G) recentl

Physical activity has numerous beneficial effects on metabolic and inflammatory processes

Obesity is a long-term multifactorial chronic disease, characterized by energy imbalance, due to an excess of caloric intake compared to energy expenditure and deregulation of other metabolic parameters, as, altered lipid profile, increased insulin resistance and chronic pro-inflammatory state. A healthy lifestyle, characterized by hypocaloric diet and physical activity, is important to reduce a chronic inflammation, oxidative stress and metabolic disorders typical of obesity. It is well known that the chronic inflammation state and oxidative stress are responsible for the aging and development of many diseases, such as cancer. In the light of these evidences, the aim of this study is to analyse body composition, metabolic profile and oxidative stress levels in obese patients subjected to a physical activity program before and after weight loss. We analysed the glycaemic and lipid profile, body composition such as visceral adipose tissue (VAT), fat mass (FM), and the dROMs serum levels via the Fenton's reaction. We found that in obese patients before physical activity intervention there are higher levels in dROMs serum levels, altered glycaemic and lipid profile and body composition compared to obese patients after physical activity intervention. In conclusion, the physical activity has numerous beneficial effects in obesity, modulating not only metabolic profile but also inflammatory and oxidative stress response

Role of Vitamin E and the Orexin System in Neuroprotection.

Microglia are the first line of defense at the level of the central nervous system (CNS). Phenotypic change in microglia can be regulated by various factors, including the orexin system. Neuroinflammation is an inflammatory process mediated by cytokines, by the lack of interaction of specific receptors such as the OX2-OX2R complex, caused by systemic tissue damage or, more often, associated with direct damage to the CNS. Chronic activation of microglia could lead to long-term neurodegenerative diseases. This review aims to explore how tocopherol (vitamin E) and the orexin system may play a role in the prevention and treatment of microglia inflammation and, consequently, in neurodegenerative diseases thanks to its antioxidant properties. The results of animal and in vitro studies provide evidence to support the use of tocopherol for a reduction in microglia inflammation as well as a greater activation of the orexinergic system. Although there is much in vivo and in vitro evidence of vitamin E antioxidant and protective abilities, there are still conflicting results for its use as a treatment for neurodegenerative diseases that speculate that vitamin E, under certain conditions or genetic predispositions, can be pro-oxidant and harmful

Guinea worm wrap-up

Sudan has reported 21,433 cases of dracunculiasis in January-July 2002, which is 73% of the global total of cases reported for that period. Whereas 36% of 8,058 endemic villages reported in January-July 2001, 62% of 6,224 endemic villages reported during the same period of 2002. The latest update on the status of the program was discussed during the annual Program Review of the Guinea Worm Eradication Programs of Sudan, Ethiopia and Uganda, which was held in Nairobi, Kenya on September 30 \ue2\u20ac\u201c October 2. The percentage of known endemic villages with nylon filters in every household increased from 29% to 58% between 2001 and 2002, and over 7 million pipe filters were distributed in 2001. Health education talks by village volunteers have increased from 50% to 83% of endemic villages, and are increasingly supplemented by radio broadcasts in local languages. Abate usage is still limited in all but the northern states of the country

Implementation of psychology counseling sufistic for diabetes genetic client in millenial age

Everyone through the millennial age. The researcher assessed that when in the millennial age, the age of approximately 24–35 if a person can successfully lead a career, economic, religious, health, family life, then in his age after millennial, she/he just reaped the success of his/her business at the next millennial age. Method: selected clients have genetic diabetics at the age of 50 years, but one of the health lives that is lived at millennial age is not well regulated, so at the age above the age of age he has genetic diabetics, especially most families also have diabetes and die on average 40 years average. Undergoing the Quran treatment that tells the story of the previous prophet‘s life in the prophet and sufistic counseling psychology is predicted to prepare the client to accept destiny as a person with genetic diabetes and prepå clients to face death. Result: Thus the success of undergoing millennial age in all predicted increases happiness in the age after millennial age. the toughness of someone living life even in severe pain is something that needs to be prepared in the treatment of Sufi counseling psychology. Sufistic counseling formula is someone trying to pray until the maximum problem results are up to God PET = R

Anabolic Androgenic Steroids: Searching New Molecular Biomarkers

Even if anabolic androgenic steroid (AAS) abuse is clearly associated with a wide spectrum of collateral effects, adolescents and athletes frequently use a large group of synthetic derivatives of testosterone, both for aesthetic uses and for improving performance. Over the last few years, the development of MicroRNA (miRNA) technologies has become an essential part of research projects and their role as potential molecular biomarkers is being investigated by the scientific community. The circulating miRNAs detection as a diagnostic or prognostic tool for the diagnosis and treatment of several diseases is very useful, because with a minimal quantity of sample (peripheral blood), miRNAs are very sensitive. Even more, miRNAs remain stable both at room temperature and during freeze-thaw cycles. These characteristics highlight the important role of miRNAs in the near future as new tools for anti-doping. The article provides a systematic review and meta-analysis on the role of miRNAs as new potential molecular biomarkers of AAS use/abuse. Particularly, this paper analyzed the “miRNA signature” use as biomarkers for health disorders, focusing on the organ damages which are related to ASS use/abuse. Moreover, this review aims to provide a future prospect for less invasive or non-invasive procedures for the detection of circulating miRNA biomarkers as doping assumption signaling

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Chemotherapy and radiotherapy for anal canal carcinoma

[No abstract available

The influence of preoperative MRI in early breast cancer: gold standard

Abstract Background: Aim of this study was to evaluate the impact of presurgical breast MRI on the surgical management of selected patients with early-stage breast cancer, who were candidates for BCT. Materials and methods: The trial was built up according to the major European Breast Society. In additional foci classified as BI-RADS 3-4 (4a, 4b, and 4c), a targeted second-look US study was performed. Results: A total of 123 patients underwent presurgical breast MRI. Therapeutic strategy established based on MRI was appropriate in 83.8% of cases. Analysis carried out on the subgroup of patients with dense breast showed that additional foci were found in 41.9% and a greater local extension of the index lesion in 6.4%. Conclusion: The results obtained in the subgroup of patients with high breast density suggest the importance of a sensitive tool such as MRI in the local staging of breast cancer before treatment planning

Preoperative intensified radiochemotherapy for rectal cancer: experience of a single institution

The aim of our study was to evaluate the feasibility and the effectiveness of an intensified neoadjuvant protocol with the addition of weekly oxaliplatin in the preoperative strategy of rectal cancer treatment. Patients with locally advanced rectal cancer received continous infusion 5-Fluorouracil (5-FU) 200 mg/m(2)/day in combination with weekly oxaliplatin at a dose of 50 mg/m(2). Doses of radiotherapy were 45 Gy to the whole pelvis plus 5.4-9 Gy to the tumour mass. The primary end-points of the study were evaluation of toxicity, compliance with radiotherapy and chemotherapy, downstaging, pathological complete response (pCR) and the rate of sphincter preservation for distal cancers. Secondary end-points were relapse-free and overall survival. From November 2006 to June 2009, 51 patients were enrolled into the study. Compliance with chemotherapy was 80%. The incidence of G3 diarrhoea and proctitis were 17.6% and 21.5%, respectively. Surgery was performed in 48 patients with 100% R0 resection. 76.4% of low-lying tumours underwent conservative treatment. Seventy-nine percent of patients were downstaged: T and N downstaging were observed in 71% and 75% of patients, respectively. A pCR was obtained in 11 (22.9%) patients. Intensification of neoadjuvant treatment for rectal cancer with the addition of weekly oxaliplatin is feasible, with remarkable rates of downstaging and pathological complete response. Data on sphincter preservation for distal cancers were excellent. Phase III trials with a longer follow-up will establish whether this good outcome in terms of surrogate end-points will translate into better rates of disease-free and overall survival